Multiparticulate oral dosage form providing prolonged release of tapentadol

Abstract

The invention relates to an oral pharmaceutical dosage form comprising a plurality of coated particles, wherein said coated particles comprise a core which comprises a Tapentadol component and which is coated with a controlled release coating material, wherein the controlled release coating material comprises a lubricant component and a polymer component, wherein the polymer component comprises one or more cellulose ethers and/or one or more acrylates, and wherein the pharmaceutical dosage form provides controlled release of the Tapentadol component.

1 . An oral pharmaceutical dosage form comprising a plurality of coated particles, wherein said coated particles comprise a core which comprises a Tapentadol component, wherein under in vitro conditions the pharmaceutical dosage form provides controlled release of the Tapentadol component, and wherein the core is coated
 (i) with a controlled release coating material, wherein the controlled release coating material comprises a lubricant component and a polymer component, wherein the polymer component comprises one or more cellulose ethers and/or one or more acrylates; and/or   (ii) with a tamper resistant coating material providing resistance against ethanolic dose dumping.   
     
     
         2 . The dosage form according to  claim 1 , wherein the controlled release coating material essentially consists of the lubricant component and the polymer component. 
     
     
         3 . The dosage form according to  claim 1 , wherein the polymer component comprises or essentially consists of a cellulose ether selected from the group consisting of ethylcellulose, hydroxyethylcellulose, propylcellulose, hydroxypropylcellulose, hydroxypropyl methylcellulose, and mixtures thereof. 
     
     
         4 . The dosage form according to  claim 3 , wherein the cellulose ether is ethylcellulose. 
     
     
         5 . The dosage form  claim 1 , wherein the lubricant component comprises or essentially consists of a fatty acid, a metallic salt of a fatty acid, a fatty acid ester, an inorganic material, a polymeric lubricant, or a mixture thereof. 
     
     
         6 . The dosage form according to  claim 5 , wherein
 the fatty acid is selected from stearic acid, myristic acid, palmitic acid, and mixtures thereof; and/or   the metallic salt of a fatty acid is selected from magnesium stearate, calcium stearate, zinc stearate, and mixtures thereof; and/or   the fatty acid ester is selected from glyceride esters; and sugar esters; and mixtures thereof; and/or   the inorganic material is talc; and/or   the polymeric lubricant is macrogol.   
     
     
         7 . The dosage form according to  claim 1 , wherein the weight content of the controlled release coating material, relative to the total weight of the coated particles, is within the range of from 5.0 wt.-% to 21 wt.-%. 
     
     
         8 . The dosage form according to  claim 1 , wherein the coated particles comprise a core which comprises a drug coat and a controlled release coat, wherein the drug coat comprises the Tapentadol component and wherein the controlled release coat comprises the controlled release coating material. 
     
     
         9 . The dosage form according to  claim 8 , wherein the drug coat and the controlled release coat are in intimate contact with one another. 
     
     
         10 . The dosage form according to  claim 1 , wherein the coated particles have an average weight per particle within the range of 100±90 μg. 
     
     
         11 . The dosage form according to  claim 1 , wherein the relative weight ratio of the polymer component to the lubricant component is within the range of from 5.0:1.0 to 2.1:1.0. 
     
     
         12 . The dosage form according to  claim 1 , wherein the weight content of the polymer component, relative to the total weight of the coated particles, is within the range of 10.0±9.0 wt.-%. 
     
     
         13 . The dosage form according to  claim 1 , wherein the weight content of the lubricant component, relative to the total weight of the coated particles, is within the range of 3.0±2.5 wt.-%. 
     
     
         14 . The dosage form according to  claim 1 , which is a filled capsule comprising the plurality of coated particles. 
     
     
         15 . The dosage form according to  claim 14 , wherein the capsule is a sprinkle capsule. 
     
     
         16 . An oral pharmaceutical dosage form comprising a plurality of coated particles, wherein said coated particles comprise a core which comprises a Tapentadol component, wherein the core is coated with a controlled release coating comprising a controlled release coating material, wherein the controlled release coating material has a weight, relative to a total weight of the coated particles, within the range of 13.0±3.0 wt.-%, wherein the controlled release coating material comprises a lubricant component and a polymer component, wherein the polymer component comprises one or more cellulose ethers, wherein the lubricant comprises magnesium stearate, wherein a total content of lubricant and polymer content is at least 80 wt.-% relative to a total weight of the controlled release coating, wherein the polymer component and the lubricant component are present in the controlled release coating in a relative weight ratio of polymer component:lubricant component within the range of from 5.0:1 to 2.0:1.0, wherein the lubricant is present in the controlled release coating in an amount of at least 15 wt.-% relative to the total weight of the controlled release coating, wherein under in vitro conditions the pharmaceutical dosage form provides controlled release of the Tapentadol component, and wherein the pharmaceutical dosage form provides a mean T max  under fasted conditions in less than 7.0 hours following oral administration. 
     
     
         17 . A method of treating pain in a patient in need thereof, said method comprising administering to said patient at least one dosage form according to  claim 1 . 
     
     
         18 . A method of treating pain in a patient in need thereof, said method comprising administering to said patient at least one dosage form according to  claim 16 . 
     
     
         19 . A process for the manufacture of a pharmaceutical dosage form according to  claim 1 , the process comprising the step of
 (b) applying a controlled release coating material, which comprises a lubricant component and a polymer component, to a plurality of cores, which comprise a Tapentadol component.   
     
     
         20 . The process according to  claim 19 , comprising the preceding step of
 (a) applying a drug coat, which comprises the Tapentadol component, to a plurality of starter pellets thereby providing the plurality of cores.   
     
     
         21 . An oral pharmaceutical dosage form comprising a plurality of coated particles, wherein said coated particles comprise a core which comprises a Tapentadol component, wherein the core is coated with a controlled release coating comprising a controlled release coating material, wherein the controlled release coating material has a weight, relative to a total weight of the coated particles, within the range of 13.0±3.0 wt.-%, wherein the controlled release coating material comprises a lubricant component and a polymer component, wherein the polymer component comprises one or more cellulose ethers, wherein the lubricant comprises magnesium stearate, wherein a total content of lubricant and polymer content is at least 80 wt.-% relative to a total weight of the controlled release coating, wherein the polymer component and the lubricant component are present in the controlled release coating in a relative weight ratio of polymer component:lubricant component within the range of from 5.0:1 to 2.0:1.0, wherein the lubricant is present in the controlled release coating in an amount of at least 15 wt.-% relative to the total weight of the controlled release coating, wherein under in vitro conditions the pharmaceutical dosage form provides controlled release of the Tapentadol component, and wherein upon administration to a human patient, the pharmaceutical dosage form is bioequivalent in at least one parameter to a monolithic tablet providing prolonged release of a Tapentadol component at the same dose. 
     
     
         22 . The dosage form according to  claim 21 , wherein the at least one parameter is C max .